The instant invention relates to a novel class of modified permeable water swellable polymers. Water swellable polymers belong to a genus of materials known as hydrogels.
Hydrogels have been described since 1965, e.g. U.S. Pat. No. 2,976,576, and subsequently a large number of patents have been issued describing the synthesis and use of hydrogels based primarily on 2-hydroxyethyl methacrylate and, to a lesser extent, on N-vinylpyrrolidone. Typically, these hydrogels are crosslinked, water-swellable polymers made by copolymerization of 2-hydroxyethyl methacrylate. They are used as polymeric, inert carriers for active substances, which are slowly and controllably released from these carriers; such active substances may be drugs as in U.S. Pat. Nos. 3,577,826; 3,577,512; 3,551,556; 3,520,949; 3,576,760; 3,641,237, and 3,660,563; 4,177,056; 4,192,827; agricultural chemicals, as in U.S. Pat. No. 3,576,260 or fragrances, as in U.S. Pat. Nos. 3,400,890; 3,567,118; and 3,697,643.
Their uses as body implants and bandages have also been described in U.S. Pat. Nos. 3,577,516; 3,695,921; 3,512,183; and 3,674,901. The widely used soft contact lens consists of this material, as in U.S. Pat. Nos. 3,488,111; 3,660,545; and 3,629,504.
In the pharmaceutical field the main interest lies in the slow and controllable release of drugs from such hydrogels. Drug-containing hydrogel preparations have been described as being in the form of bandages; subcutaneous implants, buccal devices, intrauterine devices, and eye inserts. They are made by complicated fabrication procedures which usually involves casting the monomer solution into a suitable mold and polymerizing in the presence of a free readical generating initiator.
The use of drug loaded hydrogel granules as an oral dose form has also been suggested in Australian 16202/67 and U.S. Pat. No. 4,177,056. It is indeed one of the most useful applications of this concept in medicine since it allows the delivery into the bloodstream of an orally taken drug to spread out over several hours in a reproducible manner. This eliminates wasteful and potentially dangerous peak drug concentrations in the blood, while prolonging the time during which preferred and effective drug levels in the blood are maintained.
Whenever active ingredients are released from a monolithic hydrogel matrix by diffusion in an aqueous medium, their release tends to follow first order kinetics, that is the release rate is ordinarily proportional to the drug concentration inside the gel; it is fastest at the very beginning and gradually slows down toward the end. While such a mechanism prolongs the release of an active ingredient and spreads it out long enough to make it useful for instance for orally taken drugs whose metabolic half-life in the body is in the order of several hours, it is not useful for delivering an active substance at a more constant rate, as is necessary for drugs whose metabolic half-life is short.
In such a case, the hydrogel, serving as the reservoir of the drug, has been covered by a membrane of lesser permeability, this membrane being laminated or coated on the surface of the hydrogel. Diffusion through this membrane is the release rate determining step, and the release rate itself is less influenced by the changing drug concentration in the hydrogel. Thus, the release rate follows a mechanism close to zero-order.
While such modified hydrogels containing a coated or laminated rate controlling membrane are useful, such membranes may peel off and delaminate under conditions of swelling and deswelling or simply burst due to osmotic pressure exerted by the dissolving active ingredient. For instance, plasma polymerization or plasma induced polymerization which can be used to deposit thin membranes on polymeric substrates characteristically results in brittle coatings which tend to peel off and suffer from poor adhesion, especially under conditions of volume expansion and contraction, as occurs during the swelling and drying operations.